Abstract 1445: Growth inhibitory and anti-metastatic effects of the hexane/ethanol extract of Glycyrrhiza uralensis in a mouse breast cancer xenograft model

Abstract

Abstract Glycyrrhiza uralensis (licorice) is one of the most frequently prescribed ingredients in Oriental medicine and licorice root extracts have previously been shown to exhibit anti-carcinogenic activities. However, these extracts harbor considerable quantities of glycyrrhizin, which is known to exert anticarcinogenic activities and to induce severe hypokalemia and hypertension. In this study, we evaluated the effects of the hexane/ethanol extract of Glycyrrhiza uralensis (HEGU), which lacks glycyrrhizin, on the metastatic characteristics of 4T1 murine mammary carcinoma cells. When 4T1 cells were cultured on a transwell-filter in an in vitro cell culture model, HEGU inhibited cell migration and adhesion in a dose-dependent manner. Gelatin zymography and Western blot analysis showed that HEGU significantly suppressed the secretion and activation of the matrix metalloproteinase (MMP)-2 and MMP-9. The secretion of tissue inhibitor of metalloproteinase (TIMP)-1 was reduced in HEGU-treated cells. HEGU reduced the protein levels of intercellular adhesion molecule and vascular cell adhesion molecule. To assess the effects of HEGU on lung metastasis in vivo, we injected 4T1 cells (5×104 cells) into the inguinal mammary fat pads of syngeneic, immunocompetent BALB/c mice. One week after 4T1 cell injection, the mice were given HEGU (5 mg/kg body weight/day) in the drinking water for 25 days. HEGU treatment inhibited the solid tumor growth and the number of pulmonary tumor nodules. Immunohistochemistry results revealed that HEGU treatment reduced the expression of CD31, vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen and cyclin-dependent kinase 4 in the tumor tissues. In addition, the serum concentrations of MMP-9 and VEGF were decreased in the sera of mice treated with HEGU. In the present study, we have demonstrated in both in vivo and in vitro systems that HEGU greatly inhibits the growth and lung metastasis of 4T1 cells, which was accompanied by reduced levels of MMPs, adhesion molecules and VEGF. These data suggest that HEGU possesses chemotherapeutic efficacy against breast cancer including the growth of tumor and inhibition of metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1445.